A Pilot, Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of the Effects of Titrated Oral Tolvaptan 15, 30, or 60 mg QD on Cognitive and Neurological Function in Elderly Hyponatremic Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 12
- 主要终点
- Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores)
研究概览
简要总结
Demonstrate an improvement in the composite scores of validated neurocognitive tests in elderly subjects with chronic sub-clinical (i.e., asymptomatic) hyponatremia.
详细描述
Subjects will be randomized, with stratification by baseline sodium <130 or ≥ 130 mEq/L[mmol/L] to receive either tolvaptan 15 mg tablet or matching placebo tablet at doses of 15, 30 or 60 mg for 21 days. During this period, fluid restrictions should be loosened or suspended, until the subject's response to therapy can be evaluated, typically over the first few days of therapy. Fluid restriction may be reinstituted at any time in subjects whose sodium fails to improve or worsens with study therapy. A forced-titration up to 60 mg of study drug by day 3 to 7 will be based on the subject's serum sodium Subjects entering the study with a serum sodium concentration less than 130 mEq/L[mmol/L] may be fluid restricted if necessary at the discretion of the Investigator. Subjects should be monitored closely during the first 24 hours of treatment for dosing titration. The total dosing duration will be up to 21 days (plus 3 day treatment window). Subjects will return to the clinic on Day 22 (+3 days) for assessments and will complete a follow-up visit on Day 28 (+2 days).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Women and men 50 years of age or older.
- •Serum Sodium ≥123 and ≤ 134 mEq/L [mmol/L]at screening and baseline.
- •Subjects with serum sodium concentrations ≥118 and ≤122 mEq/L[mmol/L] at screening and baseline may be entered into the trial based on consultation and approval from the study medical monitor.
排除标准
- •Conditions or history which may present a safety concern to the subject or their offspring or extreme susceptibility to hypotension with sudden fluid loss (aquaresis).
- •Hyponatremia that is acute, easily reversible, artifactual, or due to a condition not associated with vasopressin excess or likely to respond to aquaretic therapy.
- •Conditions associated with an independent imminent risk of morbidity and mortality.
- •Conditions which may confound the assessment of endpoints, history of poor compliance, participation in a clinical trial believed by the PI or Sponsor likely to confound endpoint assessments.
- •Conditions which may confound primary endpoints of cognitive function.
研究组 & 干预措施
1
Placebo tablet given once a day for 21 days
干预措施: Placebo (Drug)
2
Tolvaptan 15 mg-60 mg tablet given once a day for 21 days.
干预措施: Tolvaptan (Drug)
结局指标
主要结局
Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores)
时间窗: baseline and Day 22
Change from baseline to Day 22 in sum of all speed domain Z-scores:Reaction Time (Simple=recognize "yes" 50 times;Choice=recognize "yes" or "no" 50 times;Digit Vigilance=match 45 digits);Psychomotor Speed (Morse Tapping=tap button for 30 seconds with right \& left hands);Processing Speed (Rapid Visual Information Processing=detect consecutive sequences of 3 odd or 3 even digits;Numeric Working Memory=recognize numbers from series of 5 digits among 30;Word Recognition=remember 15 prior learned words from 30 total;results age-matched to healthy controls from Cognitive Drug Research normative data
次要结局
- Change From Baseline to Day 22 in the Individual Neurocognitive Domains Included in the Primary Endpoint: Reaction Time in Computer Tests(baseline and Day 22)
- Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Psychomotor Speed Via Morse Tapping Test(baseline and Day 22)
- Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Processing Speed of Rapid Visual Information Processing Test, Numeric Working Memory Test, and Word Recognition Test(baseline and Day 22)
- Change From Baseline in Overall Neurocognitive Composite Score(baseline and Day 22)
- Change From Baseline in Gait Test (Timed Get-Up-and-Go Test)(baseline and Day 22)
- Change From Baseline in Postural Stability Test(baseline and Day 22)
- Change From Baseline in Serum Sodium; ITT Population(Baseline and Day 22)
- Number of Patients With Vital Sign Abnormalities: Blood Pressure(28 days)
- Number of Patients With Vital Sign Abnormalities: Pulse Rate(28 days)
- Number of Patients With Vital Sign Abnormalities: Body Weight(28 days)
- Number of Patients With Vital Sign Abnormalities: Body Temperature(28 days)
- Number of Patients With Hematology Laboratory Abnormalities: Hemoglobin(28 days)
- Number of Patients With Hematology Laboratory Abnormalities: Activated Partial Thromboplastin Time (aPTT)(28 days)
- Number of Patients With Hematology Laboratory Abnormalities: Lymphocytes(28 days)
- Number of Patients With Hematology Laboratory Abnormalities: Neutrophils(28 days)
- Number of Patients With Serum Chemistry Laboratory Abnormalities: Blood Urea Nitrogen (BUN)(28 days)
- Number of Patients With Serum Chemistry Laboratory Abnormalities: Uric Acid(28 days)
- Number of Patients With Serum Chemistry Laboratory Abnormalities: Cholesterol(28 days)
- Number of Patients With Serum Chemistry Laboratory Abnormalities: Glucose(28 days)
- Number of Patients With Serum Chemistry Laboratory Abnormalities: Magnesium(28 days)
- Number of Patients With Electrocardiogram (ECG) Abnormalities: QT >500 Milliseconds (Msec)(28 days)
- Number of Patients With Electrocardiogram (ECG) Abnormalities: QRS Interval(28 days)
- Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcB Increase 30-60 Msec(28 days)
- Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcF Increase 30-60 Msec(28 days)
- Number of Patients With Electrocardiogram (ECG) Abnormalities: ST Segment(28 days)
- Number of Patients With Electrocardiogram (ECG) Abnormalities: T Wave(28 days)
- Number of Patients With Electrocardiogram (ECG) Abnormalities: Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)(28 days)
- Number of Patients With Electrocardiogram (ECG) Abnormalities: Arrhythmia(28 days)